Uniaxial Cyclic Stretching Promotes Chromatin Accessibility of Gene Loci Associated With Mesenchymal Stem Cells Morphogenesis and Osteogenesis

Zhang, Duo; Zhang, Ran; Song, Xiaoyuan; Yan, Karen Chang; Liang, Haiyi

doi:10.3389/fcell.2021.664545

Cited by 11 publications

(12 citation statements)

References 88 publications

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“…In turn, this results in altered nuclear morphology. The altered nuclear morphology can change chromatin conformation allowing access to the promoter region of certain genes [33]. We suspect that access to the Mmp3 promoter region is altered, however, this was not tested here and is a matter of future investigation.…”

Section: Discussionmentioning

confidence: 96%

The application of mechanical load onto mouse tendons by magnetic restraining represses Mmp-3 expression

Mousavizadeh

West

Inguito

et al. 2022

Preprint

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Objectives: Mechanical loading is crucial for tendon matrix homeostasis. Under-stimulation of tendon tissue promotes matrix degradation and ultimately tendon failure. In this study, we examined the expression of tendon matrix molecules and matrix-degrading enzymes (matrix metalloproteinases) in stress-deprived tail tendons and compared to tendons that were mechanically loaded by a simple restraining method. Data description: Isolated mouse tail fascicles were either floated or restrained by magnets in cell culture media for 24 hours. The gene expression of tendon matrix molecules and matrix metalloproteinases in the tendon fascicles of mouse tails were examined by real-time RT-PCR. Stress deprivation of tail tendons increase Mmp3 mRNA levels. Restraining tendons represses these increases in MMP3. The gene expression response to restraining was specific to Mmp3 at 24 hours as we did not observe mRNA level changes in other matrix related genes that we examined (Col1, Col3, Tnc, Acan, and Mmp13). To elucidate, the mechansims that may regulate load transmission in tendon tissue, we examined filamentous (F-)actin staining and nuclear morphology. As compared to stress deprived tendons, restrained tendons had greater staining for F-actin. The nuclei of restrained tendons are smaller and more elongated. These results indicate that mechanical loading regulates specific gene expression potentially through F-actin regulation of nuclear morphology. A further understanding on the mechanisms involved in regulating Mmp3 gene expression may lead to new strategies to prevent tendon degeneration.

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Section: Discussionmentioning

confidence: 96%

The application of mechanical load onto mouse tendons by magnetic restraining represses Mmp-3 expression

Mousavizadeh

West

Inguito

et al. 2022

Preprint

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“…Nevertheless, on flat substrates, similar low strain regimes induce prominent cellular mechanoresponses. For instance, uniaxial strain (8%, 1 Hz) triggered actin cytoskeleton reorientation, modulation of pathways involved in cell-matrix adhesion and osteogenic differentiation in human mesenchymal stem cells ( Zhang et al, 2021 ). Moreover, uniaxial strain (14%, 0.3 Hz) induced reorganization of mechanoresponsive focal adhesions and adherence junctions in differentiating epithelial skin cells ( Noethel et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development

Friedland

Babu

Springer

et al. 2022

Front. Cell Dev. Biol.

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Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore, we created a magnetic shear strain device that enabled, for the first time, to analyze the instant shear strain response of human breast gland cells. MCF10A-derived breast acini with basement membranes (BM) of defined maturation state and basoapical polarization were used to resemble breast gland morphogenesis in vitro. The novel biophysical tool was used to apply cyclic shear strain with defined amplitudes (≤15%, 0.2 Hz) over 22 h on living spheroids embedded in an ultrasoft matrix (<60 Pa). We demonstrated that breast spheroids gain resistance to shear strain, which increased with BM maturation and basoapical polarization. Most intriguingly, poorly developed spheroids were prone to cyclic strain-induced extrusion of apoptotic cells from the spheroid body. In contrast, matured spheroids were insensitive to this mechanoresponse—indicating changing mechanosensing or mechanotransduction mechanisms during breast tissue morphogenesis. Together, we introduced a versatile tool to study cyclic shear stress responses of 3D cell culture models. It can be used to strain, in principle, all kinds of cell clusters, even those that grow only in ultrasoft hydrogels. We believe that this approach opens new doors to gain new insights into dynamic shear strain-induced mechanobiological regulation circuits between cells and their ECM.

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“…Furthermore, stretch can promote angiogenesis by chromatin reorganization ( Figure 4 ). Cell stretching results in a change in chromatin architecture which promotes chromatin accessibility ( Nava et al, 2020 ; Zhang et al, 2021 ). The changes to chromatin can directly influence transcription ( Nava et al, 2020 ).…”

Section: Mechanotransduction In Response To External Force and The Im...mentioning

confidence: 99%

Mechanical regulation of signal transduction in angiogenesis

Flournoy

Ashkanani

Chen

2022

Front. Cell Dev. Biol.

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Biophysical and biochemical cues work in concert to regulate angiogenesis. These cues guide angiogenesis during development and wound healing. Abnormal cues contribute to pathological angiogenesis during tumor progression. In this review, we summarize the known signaling pathways involved in mechanotransduction important to angiogenesis. We discuss how variation in the mechanical microenvironment, in terms of stiffness, ligand availability, and topography, can modulate the angiogenesis process. We also present an integrated view on how mechanical perturbations, such as stretching and fluid shearing, alter angiogenesis-related signal transduction acutely, leading to downstream gene expression. Tissue engineering-based approaches to study angiogenesis are reviewed too. Future directions to aid the efforts in unveiling the comprehensive picture of angiogenesis are proposed.

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Uniaxial Cyclic Stretching Promotes Chromatin Accessibility of Gene Loci Associated With Mesenchymal Stem Cells Morphogenesis and Osteogenesis

Cited by 11 publications

References 88 publications

The application of mechanical load onto mouse tendons by magnetic restraining represses Mmp-3 expression

The application of mechanical load onto mouse tendons by magnetic restraining represses Mmp-3 expression

ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development

Mechanical regulation of signal transduction in angiogenesis

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